Intramolecular Iron-Mediated C–H Bond Heterolysis with an Assist of Pendant Base in a [FeFe]-Hydrogenase Model

Although
many metalloenzymes containing iron play a prominent role
in biological C–H activation processes, to date iron-mediated
C­(sp3)–H heterolysis has not been reported for synthetic
models of Fe/S-metalloenzymes. In contrast, ample precedent has established
that nature’s design for reversible hydrogen activation by
the diiron hydrogenase ([FeFe]-H2ase) active site involves
multiple irons, sulfur bridges, a redox switch, and a pendant amine
base, in an intricate arrangement to perform H–H heterolytic
cleavage. In response to whether this strategy might be extended to
C–H activation, we report that a [FeFe]-H2ase model
demonstrates iron-mediated intramolecular C–H heterolytic cleavage
via an agostic C–H interaction, with proton removal by a nearby
pendant amine, affording FeII–[Fe′II–CH–S] three-membered-ring
products, which can be reduced back to 1 by Cp2Co in the presence of HBF4. The function of the pendant
base as a proton shuttle was confirmed by the crystal structures of
the N-protonated intermediate and the final deprotonated product in
comparison with that of a similar but pendant-amine-free complex that
does not show evidence of C–H activation. The mechanism of
the process was backed up by DFT calculations.